ONITT: Study of Onivyde with Talazoparib or Temozolomide in Children and Young Adults with Recurrent/Refractory Solid Tumors and Ewing Sarcoma

This is a phase 1/2 study to evaluate onivyde plus talazoparib or temozolomide in pediatric patients with recurrent/refractory solid tumors and Ewing sarcoma.

Onivyde is irinotecan that has been encapsulated into a liposomal drug delivery system to increase intratumoral drug exposure while decreasing system toxicities. Talazoparib is a highly potent, orally bioavailable small molecule inhibitor of PARP1 and 2 and has significant activity in cancer cell lines with DNA damage repair deficiencies. In vitro and in vivo studies of PARP inhibitors with or without chemotherapy demonstrated significant activity against Ewing sarcoma.

In phase 1 of this study, patients with recurrent/refractory solid tumors will be randomized to Arm A (onivyde plus talzaoparib) or Arm B (onivyde plus temozolomide). Once the recommended phase 2 doses are determined, expansion cohorts will open for enrollment of non-Ewing sarcoma solid tumor patients. Concurrently, the phase 2 study will open to patients with recurrent/refractory Ewing sarcoma. Patients in phase 2 will be randomized to receive one of the two regimens.

Primary Objective

• Phase 1: To determine the recommended phase 2 doses of onivyde combined with talazoparib (Arm A) and onivyde combined with temozolomide (Arm B) in children, adolescents and young adults with refractory or recurrent solid tumors
• Phase 2: To compare the progression-free survival of onivyde plus talazoparib and onivyde plus temozolomide in patients with refractory or recurrent Ewing sarcoma

Eligibility Criteria

Inclusion criteria include:

• At least 12 months old and 30 years or younger
• Diagnosed with recurrent or refractory non-central nervous system (CNS) solid tumors (Phase 1)
• Diagnosed with recurrent or refractory Ewing sarcoma (during or after completion of first-line therapy) with EWSR1-FLI1 translocation or other EWS rearrangement (Phase 2)
• Adequate organ and bone marrow function

Exclusion Criteria include:

• Pregnant or breastfeeding
• Use of other investigational drugs while on the study
• Treatment within last 7 days prior to enrollment with food or drugs known to be strong CYP3A4 inhibitors
• Treatment within last 7 days prior to enrollment with drugs known to be strong CYP3A4 inducers
• Treatment within last 7 days prior to enrollment with drugs known to be potent P-gp inhibitors
• Previous treatment with talazoparib or onivyde (Phase 1)
• Progression on a PARP inhibitor plus irinotecan-containing regimen
• Previous treatment with talazoparib, onivyde or temozolomide (Phase 2)

Study Sites

St. Jude Children’s Research Hospital
Memphis, Tennessee

Collaborating sites in and outside the U.S.

About this study

This is a research study of a drug called onivyde  (liposomal irinotecan) in combination with the drugs talazoparib or temozolomide. All three drugs are approved by the Food and Drug Administration (FDA) for the treatment of other cancers. The treatment in this study is considered experimental because it has not been proven to work in children and young adults with solid tumors or Ewing sarcoma. We are studying this combination because it seems to work against cancer in the laboratory and animals. This combination has not been tested in children.

If you are accepted to this study, you or your child will receive one of two treatments:

1. Onivyde + Talazoparib (Arm A), or
2. Onivyde + Temozolomide (Arm B)

Because there is not much information about this treatment’s effect on cancers in humans, we do not know if you will benefit from taking part in this study. However, what we learn from this study may help future patients with cancer.

Purpose of this clinical trial

The main goal of this study is to test new experimental drugs in hopes of finding a treatment that may work against tumors that have come back or that have not responded to standard therapy in children, adolescents and young adults.

Eligibility overview

• At least 12 months old and 30 years or younger
• Diagnosed with recurrent or refractory solid tumor (Phase 1)
• Diagnosed with recurrent or refractory Ewing sarcoma (Phase 2)